16-2431103-C-G

Variant names:

• chr16-2431103-C-G
• rs9936014
• NM_001761.3:c.17-27C>G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001761.3(CCNF):​c.17-27C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00769 in 1,610,384 control chromosomes in the GnomAD database, including 644 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.037 (345 hom., cov: 31)
  • Exomes 𝑓: 0.0046 (299 hom.)
• Consequence: CCNF NM_001761.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0130

Genes affected

CCNF (HGNC:1591): (cyclin F) This gene encodes a member of the cyclin family. Cyclins are important regulators of cell cycle transitions through their ability to bind and activate cyclin-dependent protein kinases. This member also belongs to the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of the ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbxs class and it was one of the first proteins in which the F-box motif was identified. [provided by RefSeq, Jul 2008]

ENSG00000285970 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 1 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 16-2431103-C-G is Benign according to our data. Variant chr16-2431103-C-G is described in ClinVar as [Benign]. Clinvar id is 1231346.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCNF	NM_001761.3	c.17-27C>G		intron_variant	Intron 1 of 16	ENST00000397066.9	NP_001752.2
CCNF	NM_001323538.2	c.-801-27C>G		intron_variant	Intron 1 of 15		NP_001310467.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCNF	ENST00000397066.9	c.17-27C>G		intron_variant	Intron 1 of 16	1	NM_001761.3	ENSP00000380256.4
CCNF	ENST00000293968.11	n.17-27C>G		intron_variant	Intron 1 of 15	1		ENSP00000293968.7
ENSG00000285970	ENST00000648756.1	n.562G>C		non_coding_transcript_exon_variant	Exon 3 of 3
CCNF	ENST00000569093.1	n.50-27C>G		intron_variant	Intron 1 of 3	2

Frequencies

GnomAD3 genomes AF: 0.0372 AC: 5640 AN: 151580 Hom.: 339 Cov.: 31

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0202

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000416

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00143

Gnomad OTH AF: 0.0308

GnomAD3 exomes AF: 0.0108 AC: 2694 AN: 250168 Hom.: 146 AF XY: 0.00775 AC XY: 1048 AN XY: 135260

Gnomad AFR exome AF: 0.126

Gnomad AMR exome AF: 0.0112

Gnomad ASJ exome AF: 0.00598

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000296

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00143

Gnomad OTH exome AF: 0.00754

GnomAD4 exome AF: 0.00460 AC: 6707 AN: 1458686 Hom.: 299 Cov.: 30 AF XY: 0.00398 AC XY: 2890 AN XY: 725764

Gnomad4 AFR exome AF: 0.125

Gnomad4 AMR exome AF: 0.0121

Gnomad4 ASJ exome AF: 0.00629

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000326

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.00101

Gnomad4 OTH exome AF: 0.0109

GnomAD4 genome AF: 0.0374 AC: 5675 AN: 151698 Hom.: 345 Cov.: 31 AF XY: 0.0359 AC XY: 2660 AN XY: 74112

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.0202

Gnomad4 ASJ AF: 0.00749

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000416

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00143

Gnomad4 OTH AF: 0.0304

Alfa AF: 0.0194 Hom.: 26

Bravo AF: 0.0427

Asia WGS AF: 0.00866 AC: 30 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 21, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.60
DANN	Benign	0.40
BranchPoint Hunter		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9936014; hg19: chr16-2481104;